Efficacy and safety of application of Sivelestat in pediatric intensive care unit: a systematic review and meta‑analysis.

Background: The use of Sivelestat in pediatrics remains controversial. Given the limited available evidence, drug labeling does not recommend its administration in children, yet it is increasingly used off-label for pediatric patients with cardiopulmonary bypass (CPB)-related injury or acute respiratory distress syndrome (ARDS). This meta-analysis synthesized the existing data to evaluate the efficacy and safety of Sivelestat in pediatric populations, aiming to provide evidence for rational clinical medication. Methods: A computerized search was conducted to identify reports on the application of Sivelestat in critically ill pediatric patients in databases PubMed, Embase, Cochrane Library, Web of Science, China national knowledge infrastructure (CNKI), Wanfang Data and VIP from inception to May 2026. The meta-analysis was performed using Review Manager 5.3 version. The risk of bias was assessed using the Cochrane Handbook Risk of Bias Assessment tool. Results: Finally, 8 controlled studies and 5 case reports were included, involving a total of 608 and 10 children respectively. The results of the meta-analysis showed that the overall P/F ratio was significantly higher in the SE group than in the control group [mean difference (MD) =27.17, 95% confidence interval (CI): 11.84, 42.50, P<0.001]. However, subgroup analysis revealed no significant difference in P/F ratio between the two groups among children with CPB. In children with ARDS, a marked increase in the P/F ratio was observed in the SE group [MD =24.65, 95% CI: 18.12, 31.19, P<0.001). A low risk of bias was identified for this outcome, and further research is warranted to confirm the results. The overall ICU stay time was significantly shorter in the SE group [MD =-2.57, 95% CI: -4.26, -0.87, P=0.003). Similarly, subgroup analysis showed no significant difference in children with CPB, while a marked reduction in ICU stay was observed in the SE group among children with ARDS [MD =-4.03, 95% CI: -7.12, -0.94, P=0.01). The hospital stay time was significantly shorter in the SE group [MD =-2.96, 95% CI: -3.68, -2.24, P<0.001). The overall levels of inflammatory factors were significantly lower in the SE group, including WBC count, CRP, IL-6, IL-8, and TNF-α. Among them, the subgroup findings for WBC and TNF-α were inconsistent. Only a marked reduction was found in children with ARDS. Furthermore, its incidence of complications and adverse events was significantly lower [OR =0.38, 95% CI: 0.22, 0.65, P<0.001). However, existing data are insufficient for a full safety assessment. Conclusions: In pediatric patients with severe conditions such as ALI/ARDS, Sivelestat may improve the oxygenation index and inhibit the release of inflammatory mediators, but safety assessment remains limited. However, given the limited number of included studies and inter-study heterogeneity, large-scale trials are still needed to verify the results.